A human cDNA encoding the LIM domain containing 194 amino acid cysteine and glycine rich protein 3 (CSRP3) was identified as a BAX suppressor in yeast and a pro-survival sequence that abrogated copper mediated regulated cell death (RCD). Yeast lacks a CSRP3 orthologue but it has four LIM sequences, namely RGA1, RGA2, LRG1 and PXL1. These are known regulators of stress responses yet their roles in RCD remain unknown. Given that LIMs interact with other LIMs, we ruled out the possibility that overexpressed yeast LIMs alone could prevent RCD and that CSRP3 functions by acting as a dominant regulator of yeast LIMs. Of interest was the discovery that even though yeast cells lacking the LIM encoding PXL1 had no overt growth defect, it was nevertheless supersensitive to the effects of sublethal levels of copper. Heterologous expression of human CSPR3 as well as the pro-survival 14-3-3 sequence corrected this copper supersensitivity. These results show that the pxl1∆-copper synthetic lethality is likely due to the induction of RCD. This differs from the prevailing model in which synthetic lethality occurs because of specific defects generated by the combined loss of two overlapping but non-essential functions.

中文翻译：

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用生存前序列纠正合成致死性实例。

编码包含194个氨基酸的半胱氨酸和富含甘氨酸的蛋白质3（CSRP3）的LIM结构域的人类cDNA被鉴定为酵母中的BAX抑制剂和废除铜介导的调节性细胞死亡（RCD）的存活序列。酵母缺乏CSRP3直系同源物，但它具有四个LIM序列，即RGA1，RGA2，LRG1和PXL1。这些是已知的压力反应调节剂，但它们在RCD中的作用仍然未知。考虑到LIM与其他LIM相互作用，我们排除了单独过度表达的酵母LIM可以预防RCD以及CSRP3通过充当酵母LIM的主要调节剂来发挥作用的可能性。有趣的发现是，即使缺少编码PXL1的LIM的酵母细胞也没有明显的生长缺陷，但它对亚致死水平的铜的影响却非常敏感。人CSPR3的异源表达以及促存活的14-3-3序列纠正了这种铜超敏性。这些结果表明，pxl1Δ-铜的合成杀伤力可能是由于RCD的诱导。这与流行的模型不同，在流行的模型中，由于两个重叠但非必要功能的组合损失而产生的特定缺陷，导致了合成杀伤力的发生。